Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed 9-24-25 has been entered.
Applicant’s amendments and remarks filed in conjunction with the RCE are acknowledged.
The prior rejection under 35 USC § 112(a) has been withdrawn in view of applicant’s claim amendments and remarks.
Upon reconsideration the 6-26-24 restriction requirement between the inventions of Groups I and II has been withdrawn.
Claims 1, 17, 19, 25, 27, 32, 37, 60, 67, 84, 109-118 are pending and under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 114-118 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating cancer in a patient in need thereof, said patient having NY-ESO-1 expressing melanoma cells, and said patient having the HLA-C*03 allele, comprising administering the cell of claim 67, does not reasonably provide enablement for treating any cancer by administering the cells of claim 67, including wherein the cancer is selected from the group consisting of melanoma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, non-Hodgkin's lymphoma (NHL), primary mediastinal large B cell lymphoma (PMBC), diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), transformed follicular lymphoma, splenic marginal zone lymphoma (SMZL), cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, chronic or acute leukemia, acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia (ALL) (including non T cell ALL), chronic lymphocytic leukemia (CLL), solid tumors of childhood, lymphocytic lymphoma, cancer of the bladder, cancer of the kidney or ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid cancer, squamous cell cancer, T-cell lymphoma, environmentally induced cancers including those induced by asbestos, other B cell malignancies, and combinations of said cancers.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The instant specification discloses isolation of the TCR of the claims from the tumor infiltrating lymphocytes (TIL) of a metastatic melanoma patient, and further teaches how said TIL recognizes SEQ ID NOs: 35, 36 and 37 which comprise the “minimal epitope” of amino acids 92-100 of NY-ESO-1, “LAMPFATPM” (SEQ ID NO: 13)(see Example 1). In this same example it is described how ectopic expression of HLA-C*03:04 in the A375 and SK-MEL-37 melanoma cells lines allowed said cell lines to be recognized by T cells transduced with a TCR of the instant claims. Likewise, a melanoma cell line that lacks endogenous expression of NY-ESO-1 was shown to became reactive with a T cell expressing the claimed TCR when transduced with full length NY-ESO-1 (see Example 1).
The specification further discloses the treatment of a large variety of cancer types by administering cell comprising the TCR of the instant claims (see e.g.., at page 8 paragraph 33, see also instant claims 115-118).
While the teachings of the instant specification are sufficient to enable the skilled artisan to treat cancer in a patient in need thereof, said patient having NY-ESO-1 expressing melanoma cells, and said patient having the HLA-C*03 allele, comprising administering the cell of claim 67, the teachings of the instant specification are insufficient to enable the skilled artisan to treat the vast breadth of cancers recited for example in claim 115 using the cells of claim 67.
Consistent with the teachings of the specification, the prior art recognized that a melanoma cell line expressing NY-ESO-1 was susceptible to elimination by cytotoxic lymphocytes (CTL) having LAMPFATPM-specificity (see Gedye et al., 20100068142, cited herewith, see paragraph 0042 and 0204); however, neither the instant specification nor the prior art provide sufficient direction or guidance for the skilled artisan to successfully treat the vast breath of cancers recited in the instant claims in the absence of undue experimentation.
One reason this is so was because it was known in the art prior to applicant's date of invention that different APC have the potential to present different class I MHC peptides, even when supplied with the same cDNA, in part because different cell types possess variable protein processing capabilities dependent on the proteasome(s) they express (see, e.g., Chapiro et al., J Immunol 2006; 176:1053-1061, at Discussion, especially in the summarizing final paragraph of the Discussion, cited herewith).
A more detailed description of the complexity and unpredictability associated with proteolytic processing of intracellular antigens to generate MHC class I peptides is described by Lauemøller et al. (Rev Immunogenetics 2001: 3: 00–00, renumbered as 1-15, cited herewith), at page 9, last full paragraph – page 9-10 bridging paragraph, emphasis added:
“Although the selectivity of peptide binding to MHC class I far outweighs that of peptide generation by antigen processing, the latter is still of considerable interest. As many as four out of every five peptides do not make it through antigen processing and are never offered to MHC class I (3). The overall prediction of immunogenicity could be improved if these processes could be described and predicted.
Within the MHC class I pathway, antigen processing includes several consecutive steps, which generate and transport peptides of the appropriate sizes. Firstly, native proteins antigens, perhaps
mostly those copies that are defective and/or misfolded (48), are ubiquitinated and thereby targeted for degradation by the 26S proteasome (reviewed in 4). This is a multicatalytic complex with several distinct sub-specificities including patterns where cleavage occurs after hydrophobic residues (chymotrypsin-like activity), after basic residues (trypsin-like activity) and after acidic residues. In reality, it is a longer sequence surrounding the cleavage site, which is recognized by the proteasome. Thus, there are several complicated cleavage patterns of the 26S proteasome. Adding to the complexity, the composition, activity and specificity of the proteasome is influenced by IFN-γ, leading to a shift from a constitutive to an immune cleavage pattern. The differences between these two proteasome cleavage patterns may be highly relevant; a vaccine candidate against an infectious microorganism should fit the immune cleavage pattern, whereas a tumor vaccine candidate might fit the constitutive cleavage pattern better (49). The proteasome is not the only proteolytic activity involved in epitope generation. Work from Ken Rock suggest that there is sufficient amino peptidase activity to perform extensive N-terminal trimming of proteasome generated peptides (50). In contrast, there is very little carboxypeptidase activity, which can assist in performing C-terminal trimming.
Thus, there is no requirement for the proteasome to generate the N-terminus of an epitope, whereas there is a stringent requirement for the proteasome to generate the C-terminus directly. Obviously, the epitope itself should not be degraded by the proteasome.”
Given the above it would not be clear to the skilled artisan, and undue trial and error experimentation would be required of the skilled artisan to identify which of the many varieties of cancers / tumors encompassed in the breadth of the instant claims will express NY-ESO-1, and importantly, which of said NY-ESO-1+ cancers / tumors will process NY-ESO-1 in a way that produces the requisite SEQ ID NO: 13 on the surface of said cancer / tumor in the presence of HLA-C*03 to a level sufficient for cytotoxic lymphocytes expressing to treat cancer by killing sufficient number of cancer / tumor cells expressing HLA-C*03:SEQ ID NO: 13 on their cell surface.
In sum, in view of the quantity of experimentation necessary, the limited working examples, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breadth of the claims, it would take undue trial and error experimentation to practice the claimed invention.
Claims 1, 17, 19, 25, 27, 32, 37, 60, 67, 84 and 109-113 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY S SKELDING whose telephone number is (571)272-9033. The examiner can normally be reached M-F 9-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel E Kolker can be reached at 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY S SKELDING/Primary Examiner, Art Unit 1644